1. Field of the Invention
This invention relates to a filled container with plural contents sealed within compartments in a manner isolated from each other, and more specifically to a filled and sealed, self-contained mixing container with plural contents, which contain components susceptible to mutual reaction, sealed therein in a mutually-isolated manner in advance, said container permitting simple and easy mixing of the plural contents without exposure to the external atmosphere upon use.
The container is suited particularly as a deformable container filled with plural drug preparations containing components susceptible to mutual reaction, such as medical fluids for intravenous hyperalimentation (IVH) or components for elemental diet (hereinafter abbreviated "ED"), said solutions or components being useful in a closed therapy system.
2. Description of the Related Art
There is a longstanding demand for containers which permit mixing of two types of drugs or the like in a self-contained manner immediately before use. This demand is especially strong, e.g., for heating or cooling media making us of reaction heat available upon mixing of two substances or for foods or drugs many of which tend to vary in nature if their ingredients or components are fed as a mixture to the production lines or are stored as a mixture over a long time.
Among these, drugs are each composed of plural chemical substances. Many of such drugs therefore tend to undergo variations with the passage of time if such chemical substances are subjected as a mixture to a heat-treatment step or are stored as a mixture over a long time.
For example, medical fluids for intravenous hyperalimentation which has been increasingly practiced in recent years are, from the above-described viewpoint, one example of drug preparations which generally are unsuited to formulation into single-pack preparations.
Intravenous hyperalimentation is applied where oral administration is insufficient or impossible as in the case of a ruptured suture in digestive tracts or problems of passage through digestive tracts, where oral administration is not preferred as in the case of inflammatory intestinal diseases or severe diarrhea, where high-calory replenishment exceeding replenishment per intestine is desired as in the case of extensive burns or severe multiple wounds, or where it is desired to treat a metabolic disorder caused by a disease such as hepatic insufficiency, renal insufficiency or glycogen storage disease.
It is therefore essential that a medical fluid for intravenous hyperalimentation contains all nutrients, which are required for the body, in appropriate amounts. The medical fluid is therefore a multi-component medical fluid containing glucides, amino acids, lipids, primary electrolytes, trace elements and vitamins. In view of their compatibility, their stability in production steps and the stability of the resultant medical fluid over a prolonged period of time, it is impossible under the circumstances to formulate them into a single composite solution. For example, if glucose and amino acids are combined together and filled as a single-pack liquid preparation in a container, reactions may take place between the glucose and the amino acids during autoclave sterilization treatment or during storage so that the medical fluid may be colored or may vary in quality.
Accordingly, the following three methods are now employed:
(1) A commercially-available base solution for intravenous hyperalimentation is used, which is a solution obtained by adding primary electrolytes to a high-concentration glucose solution. Before use, amino acids are added, followed by the addition of vitamins and any electrolytes for which reinforcement is required.
(2) A hypertonic glucose solution and an amino acid solution, which are both available on the market, are administered after mixing them together or by connecting them together.
(3) A base solution for intravenous hyperalimentation or a glucose solution is prepared by a hospital or clinic itself in its manufacturing laboratory.
Whichever method is used, it is the current situation that an amino acid solution is mixed in a base solution for intravenous hyperalimentation or a hypertonic glucose solution at the time of use and the resultant mixture is then administered to a patient.
A drug preparation which tends to lose stability when stored in the form of a solution, like ED, and cannot therefore be stored over a prolonged period of time is stored by dividing it into a powder drug portion and a liquid drug portion. These two portions are combined together immediately before use, followed by administration to a patient.
The method in which two or more components are mixed together at the time of use as described above needs a complex operation with the result that it has the potential danger of induction of preparation errors. In addition, the mixing cannot be performed in any complete closed system so that from the standpoint of safety for the hospital infection the above method also lacks adequate protection. There is accordingly a strong demand for a container which permits mixing by a simple operation in a complete closed system immediately before use.
Further, with the ever-increasing interest in home health care in recent years, there is also a desire for the development of a system which permits fail-free sure mixing of plural medicinal components so that transfusion or the like can be easily practiced at home in the future.
Filled and sealed, self-contained mixing containers have recently been put on the market, in each of which plural compartments are connected together, the points of connection are provided with isolation means capable of communicating the plural compartments to each other, and the isolation means is manipulated immediately before use to communicate the plural compartments to each other so that plural drug components filled in the plural compartments can be mixed in one of the compartments.
Conventionally known isolation means include plugs and clips. In the case of a plug, it is provided fixedly at an isolating portion dividing a single container into plural compartments. At the time of use, the plug is broken from the outside of the container to communicate the plural compartments to each other. When a clip is employed, an isolating portion dividing a single container into plural compartments is partly opened and this open portion is externally closed by the clip. The former plug method however requires arrangement of a plug, which has been fabricated separately, in a container and subsequent bonding of the plug to the container. There is hence a high potential danger that the interior of the container may be contaminated at this time. Moreover, this bonding of the plug to the container is rather difficult and a limitation may be imposed on the material. For example, to bond a three-dimensional structure such as the plug method described above, high-frequency welding is suited but heat sealing is not. Materials which can be bonded by high-frequency welding are however limited to those having a large dielectric loss such as polyvinyl chloride resin, ethylene-vinyl acetate copolymers and soft polyester resins. It has hence been difficult to use polyolefin resins for their small dielectric loss despite their high safety for the body and their low material cost.
On the other hand, the latter clip method does not permit confirmation of opening of an isolating portion even when the isolating portion is opened during transportation or storage unless such opening takes place at a time permitting its observation, for example, in use. Namely, the clip method is totally unguarded against mischief or the like. A very serious problem is therefore involved in the construction of a pharmaceutical system, for which securement of safety is a keynote, by the clip method.